Cancer Difficult to Define Classic definition tissue overgrowth

Cancer

Difficult to Define • Classic definition: tissue overgrowth which is independent of the laws governing the remainder of the body. Serves no purpose to the body. • Tumor – Original definition: mass greater than 2 cm – Neoplasm • Not all are cancer • Malignant vs. benign

Tumors • Benign – – – Grow slowly Well-defined capsule Are not invasive Well differentiated Low mitotic index Do not metastatize • Malignant – – Grow rapidly Not encapsulated Invade local tissue Anaplasia: poorly differentiated – High mitotic index – Metastasis (secondary tumor)

Cellular Adaptation • • • Atrophy Hyperplasia Metaplasia Non adaptive changes – Dysplasia – Neoplasia

Naming Cancers – Carcinoma: epithelial cells – Adenocarcinoma: glandular tissue – Sarcoma: connective tissue – Lymphoma: lymph tissue – Leukemia: blood forming tissue (marrow) – Fibroma – Osteoma – Chondroma

Tumor Markers • Chemicals produced by cancer cells – May be present in blood, CSF, or tumor cell membranes – Usually similar or same as tissues that gave rise to tumor or fetal proteins from that tissue • • • Pheochromocytoma: epinephrine Prostate cancer: prostate specific antigen (PSA) Liver cancer: alpha fetoprotein (AFP) CEA: GI tract cancers CA-124: ovarian cancers – Can be used to screen for cancer or measure success of treatment

Hallmarks of Cancer • • • Self-sufficiency in growth signals Insensitivity to antigrowth signals Evading apoptosis Limitless replicative potential Sustained angiogenesis Tissue invasion and metastasis

Carcinogenesis • Genetic – Protooncogenes – Tumor suppressor genes – Apoptosis genes – DNA repair genes • Stages – Initiation: mutation – Promotion: increased cell growth – Progression: invasiveness, angiogenesis

Protooncogenes • Vulnerable genes – Mutation causes oncogenes – New or inherited • Mutations – Point – Gene amplification – Chromosomal Rearrangement – Viral Insertion – HPV, HCV, EBV

Telomeres • End cap of chromosomes • Aging causes loss of telomere • Telomerase in germ cells (embryonic)

Factors in Cancer Development • • • Inflammation Family history: 2 possibilities Viruses Bacteria: H. pylori Environmental factors

Environmental Factors • • • Tobacco use Ionizing radiation UV radiation ETOH consumption Sexual and reproductive behavior Physical activity Occupational Air pollution EMFs Stress Diet

Cancer Mets and Staging • Common mets sites: BBLL – Brain – Bones – Liver – Lungs • Staging systems (various): carcinoma – Stage 1: confined to organ – Stage 2: locally invasive – Stage 3: lymph node invasion – Stage 4: spread to distant sites

Neoplasm-Host Interaction • Cosmetic • Tissue Compression or destruction – Ischemia – Altered or impaired function • • Increased Metabolic Demand – Cachexia Blood Supply Growth factors Immune Response

Clinical Manifestations • Pain: usually in late stage – Fear, anxiety, sleep, fatigue, culture – Likely caused by cytokine action on C/PNS • Fatigue • Cachexia (TNF-α) – Increased metabolic load – Alterations in taste – Protein degradation – ↓Low albumin, ↓clotting, ↓immune, anemia

Clinical Manifestations • Anemia – Fatigue, pallor, dyspnea on exertion • Thrombocytopenia (Platelets < 150, 000) – Bleeding • Leukopenia (WBC < 5, 000) – Infection

Cancer Treatment • Chemotherapy – Usually targets high growth cells – Single agent – Combination – Dose intensity: kill the cancer before we kill pt – Compartments: only kills mitotic cells • Cell undergoing mitosis • Cells in gap phase • Cells that do not divide

Cancer Treatment • Radiation • Surgery – Local surgery – Sentinel nodes (skip metastasis) – Debulking • Hormonal Therapy • Immunotherapy

Cancer Immunotherapy • • Immunomodulating Agents Interferons Antigens (Tumor painting) Effector Cells and lymphokines – LAK • Monoclonal Antibodies • Dendritic Cell activation

Side Effects of Cancer Treatment • Cells are same as body cells • Treatment usually causes collateral damage • GI tract: – Nausea – Stomatitis – Thrush/Diarrhea – Anorexia – Malabsorption

Side Effects • Bone marrow suppression – Anemia – Leukopenia – Thrombocytopenia • Hair and Skin • Reproductive tract – Gamete banking • Secondary tumors • Remission • “Cancer survivor”

Major Drug Classes • Cytotoxic drugs: kills quickly growing cells – Many Cytotoxic cells are so toxic, they must be handled with gloves and administered in central lines – Star: Methotrexate: mimics folic acid • Cancer cells can’t replicate DNA • Glucocorticoids: – Directly kill cancer cells of lymph tissue – Decrease nausea when combined with antiemetics – Promote appetite and sense of well-being

Major Drug Classes • Hormone Modifiers: usually antagononize sex hormones in prostate and breast cancer • Immunostimulants • Targeted drugs: target specific cancer antigens or pathways.

Diagnosis: Warning Signs • • Lump or swelling A sore that doesn't heal Recent change in a wart/mole Unusual bleeding or discharge Changes in bladder or bowel habits Nagging cough or hoarseness Difficulty in swallowing or dyspepsia

Diagnosis: Clinical Aspects • Persistence of symptoms • Cancer markers • Identification of Mass – usually radiology – X-ray, CT, MRI, nuclear scans, PET scan – Visual (-scope) • Morphologic confirmation!!!!! – Biopsy and cytology

Leukemia • Cancer of blood producing cells • Types – AML: Acute Myelogenous Leukemia – ALL: Acute Lymphocytic Leukemia – CML: Chronic Myelogenous Leukemia – CLL: Chronic Lymphocytic Leukemia • Acute: undifferentiated, rapid onset • Chronic: mature cells, slow onset

ALL • Most common child leukemia (80%) • Mortality in adults is much higher • ALL is caused by loss of differentiation – Stuck dividing, don’t leave marrow – Accumulate, crowd out other cells • Numerous subtypes based on genetic factors – Cure rate 60% to 90%

AML • Accumulation of blast cells – Replace normal RBC, granulocytes and platelets • More common as get older; peaks in 60’s

Acute Leukemia Manifestations • • • Fatigue Bleeding Infection Anorexia Spleen, liver, node enlargement CNS: H/A, vomiting, palsy, sensory impairment

Eval & Treatment • CBC with peripheral smears • Bone marrow biopsy – Sedation/Anesthetic/Analgesia – Pressure to prevent bleeding • Chemotherapy • Stem cell transplant • Supportive therapy – Transfusions, abx, allopurinol

CLL • Monoclonal expansion of B cells • Deficit in mature B cells • Accumulation of cells in marrow does not interfere with normal blood production • Most common manifestations are infections and secondary cancers • Rare under age 45

CML • Begins in a stem cell, but favors myeloid differentiation • Myeloid function is relatively normal • Manifestations similar to AML, but take longer to appear

Eval & Treatment • CBC • Bone marrow biopsy • CLL: treatment relieves symptoms but no significant increase in lifespan

Myeloma • Cancer of Plasma Cells – Increase in ? • Manifestations – – Skeletal pain Renal failure Infections Bone destruction: hypercalcemia • Eval: bone scan, CT, MRI • TX: chemotherapy and Stem cell transplant